The compound AZT (3'-azido-3'-deoxythymidine) and derivatives thereof are known to be useful for treating viral and bacterial infections, most notably in the treatment of AIDS (see, for example, U.S. Pat. Nos. 4,724,232, 4,828,838, 4,847,244, 4,874,609, 4,874,751, 4,818,750, 5,093,114 and 5,145,840). In the past, AZT has been made from an expensive starting material, thymidine (see Horwitz, J. P., et al., J. Org. Chem., 1964, 29, 2076; Maillard, M. Farag, A., Frappier, F., Florent, J. C., Grierson, D. S., Monneret, C., Tetrahedron Lett., 1989, 30, 1955; U.S. Pat. No. 5,041,543 and DE 3,705,794).
Another known approach for preparing AZT features the coupling between an azido substituted carbohydrate precursor with an activated thymine base (see, Chu, C. K., Beach, J. W., Ullas, G. V., Kosugi, Y., Tetrahedron Lett., 1988, 29, 5349; Chu, C. K., WO 9001492 A1, February 1990; Fleet, G. W. J., Son, J. C., Derome, A. E., Tetrahedron, 1988, 44, 625; Wengel, J., Pedersen, E. B., Synthesis, 1991, 451; Hager, M. W., Liotta, D. C., J. Am. Chem. Soc., 1991, 113, 5117; Jung, M. E., Gardiner, J. M., J. Org. Chem., 1991, 56, 2614; and Sugimura, H., Osumi, K., Yamazaki, T., Yamaya, T., Tetrahedron Lett., 1991, 32, 1813).
A third approach employs D-xylose (see, U.S. Pat. No. 4,916,218, Japanese Patent 63255295, European Patent 295090, and U.S. Pat. No. 4,921,950) or D-glucofuranose (see, Hrebabecky, H., Holy, A., Carbohydr. Res., 1991, 216, 179) as starting material, using the 2'-.alpha.-hydroxy group (in carboxylic ester form) to direct the base coupling to give the required .beta.-anomer. Although the glycosidic stereoselectivity of this reaction is high, the lengthy selective protection and deprotection of the sugar moieties remained a problem, in addition to the expensive reagents used in these processes.